DNA Cloning of
            <i>Plasmodium falciparum</i>
            Circumsporozoite Gene: Amino Acid Sequence of Repetitive Epitope

Enea, Vincenzo; Ellis, J M; Zavala, Fidel; Arnot, David E.; Asavanich, Achara; Masuda, Aoi; Quakyi, Isabella A.; Nussenzweig, Ruth S.

doi:10.1126/science.6204384

Cited by 233 publications

(92 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CS proteins of all malaria species contain a central segment of species-specific amino acid repeat sequences flanked by non-repeat regions [8,9]. In the case of P. falciparum, the central portion contains approximately 40 repeats of the amino acid sequence asparagin-alanine-asparagines-proline (NANP) and several asparagines-valine-aspartic acid-proline (NVDP) repeats [10]. The central repeating region contains immunodominant B-cell epitope(s) [11], whereas the majority of epitopes responsible for the induction of CD4 and CD8 T-cells are located within the flanking regions.…”

Section: Initial Circumsporozoite Protein Vaccinesmentioning

confidence: 99%

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Heppner

Kester

Ockenhouse

et al. 2005

Vaccine

178

101

View full text Add to dashboard Cite

The goal of the Malaria Vaccine Program at the Walter Reed Army Institute of Research (WRAIR) is to develop a licensed multi-antigen, multi-stage vaccine against Plasmodium falciparum able to prevent all symptomatic manifestations of malaria by preventing parasitemia. A secondary goal is to limit disease in vaccinees that do develop malaria. Malaria prevention will be achieved by inducing humoral and cellular immunity against the pre-erythrocytic circumsporozoite protein (CSP) and the liver stage antigen-1 (LSA-1). The strategy to limit disease will target immune responses against one or more blood stage antigens, merozoite surface protein-1 (MSP-1) and apical merozoite antigen-1 (AMA-1). The induction of T-and B-cell memory to achieve a sustained vaccine response may additionally require immunization with an adenovirus vector such as adenovirus serotype 35. RTS,S, a CSP-derived antigen developed by GlaxoSmithKline Biologicals in collaboration with the Walter Reed Army Institute of Research over the past 17 years, is the cornerstone of our program. RTS,S formulated in AS02A (a GSK proprietary formulation) is the only vaccine candidate shown in field trials to prevent malaria and, in one instance, to limit disease severity. Our vaccine development plan requires proof of an individual antigen's efficacy in a Phase 2 laboratory challenge or field trial prior to its integration into an RTS,S-based, multi-antigen vaccine. Progress has been accelerated through extensive partnerships with industrial, D.G. Heppner Jr. et al. / Vaccine 23 (2005) [2243][2244][2245][2246][2247][2248][2249][2250] academic, governmental, and non-governmental organizations. Recent safety, immunogenicity, and efficacy trials in the US and Africa are presented, as well as plans for the development of a multi-antigen vaccine.

show abstract

Section: Initial Circumsporozoite Protein Vaccinesmentioning

confidence: 99%

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Heppner

Kester

Ockenhouse

et al. 2005

Vaccine

178

101

View full text Add to dashboard Cite

show abstract

“…However, due to the scarcity of antigen used for both these techniques, thev were of limited applicabilitv in epidemiological studies. The cloning bf the ci&umsporozoite TCS) orotein antigen of P. falcibarum and the elucidation of its structuri (DAME et ai., 1984;ENEA et al, 1984;NUSSENZWEI~~ & NUSSEN~WEIG,~~~~) paved the way for the use of recombinant (HOFFMAN et al. 1986) and synthetic antigens (ZAV~LA er al., 1986;'CAMP: Author for correspondence: M. de S. Wijesundera, Department of Parasitology, Faculty of Medicine, Peradeniya, Sri Lanka.…”

Section: Introductionmentioning

confidence: 99%

Antibodies to Plasmodium falciparum sporozoites following a malarial outbreak in a non-endemic area of Sri Lanka

Wijesundera

Peiris

Ariyaratne

et al. 1990

Transactions of the Royal Society of Tropical Medicine and Hygi

View full text Add to dashboard Cite

An enzyme-linked immunosorbent assay (ELISA) based on the svnthetic Deutide (NANP)m was used to characterize the sporo;oGe an&bodies 'in an unusual Plasmodium falciparum outbreak in a non-malarious area in Sri Lanka. A positive antibody response was seen in 62% of patients with their first P. falciparum illness. There was no correlation between sporozoite antibodies and the antibody against blood stages, determined by immunofluorescence assay. The majority (91%) of the patients lost the antibodies to circumsporozoite (CS) protein within one year (in the absence of re-exposure). Three patients had high levels of CS antibodies even after one year, and this persistence was related to the level of the initial antibody response. In the area of the outbreak 10% of schoolchildren had antibodies to the (NANP)a peptide. 21% of the 42 children with present or past overt malaria were antibody positive. Of the children with no such background, 8% were antibody positive. The corresponding seropositivity rates for asexual blood stages were 31% and 1% for the 2 groups respectively. It is concluded that (NANP)@ ELISA is potentially a valuable tool in sero-epidemiology, particularly in situations of seasonal transmission and recurrences due to drug resistance.

show abstract

“…In the 1950s, seminal experiments by MacGregor and Cohen confirmed that antibodies were a key component of antimalarial immunity (Cohen et al 1961). In the 1960s and 70s, the first irradiated sporozoite (whole parasite) vaccine trials were conducted leading to the identification of key malaria antigens such as circumsporozoite protein (CSP) now the basis of the most developed vaccine candidate RTS,S (Clyde et al 1973;Enea et al 1984). In the last half century, with the identification of many additional antigens, animal model and clinical vaccine trials of so-called 'subunit vaccine' approaches have shown varying success (Schwartz et al 2012).…”

mentioning

confidence: 99%

Naturally acquired immunity to malaria

Barry

Hansen

2016

Parasitology

View full text Add to dashboard Cite

DNA Cloning of Plasmodium falciparum Circumsporozoite Gene: Amino Acid Sequence of Repetitive Epitope

Cited by 233 publications

References 18 publications

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

Antibodies to Plasmodium falciparum sporozoites following a malarial outbreak in a non-endemic area of Sri Lanka

Naturally acquired immunity to malaria

Contact Info

Product

Resources

About